The specific objective of the research proposed is to determine the effect of bacterial endotoxin on the resorption of viable fetal calvariae by bone marrow-derived mononuclear phagocytes (macrophage cells) in culture. In vitro studies will be undertaken to 1. assess the effect of bacterial endotoxin on the resorption of fetal calvariae derived from the C3H/HeN strain of mouse which is characterized by a profound resistance to endotoxin (8); and 2. assess the effect of endotoxin on the resorption of calvarial explants (C3H/HeJ mouse origin) co-cultured with bone marrow-derived mononuclear phagocytes obtained from endotoxin-responsive C3H/HeJ mice. In an effort to clarify the specific mechanisms underlying any apparent change in the bone resorbing activity exhibited by bone marrow-derived cells subsequent to endotoxin treatment, additional studies will: 3. quantitate the appearance of multinucleated cells associated with calvarial explants obtained from untreated and endotoxin-treated co-cultures; and 4. analyze the effect of endotoxin on the secretion of lysosomal enzymes, i.e., collagenase, cathepsin D, acid phosphatase and B-glucuronidase, by bone marrow-derived cells in co-culture.